Membrane Lipids

Naturally occurring lipids can be divided essentially in two groups:
1. phospholipids containing glycerophosphate as the anchor group for fatty acids, and
2. lipids containing backbones other than glycerol. Phospholipids may be further subdivided into nitrogen-containing lipids, such as phosphatidylcholine (PC), -ethanolamine (PE), -serine (PS), and plasmalogens, and nitrogen-lacking lipids, such as phosphatidic acid (PA), phosphatidylglycerols (PG), cardiolipin (CL), and phosphoinositols (PI).

Examples for lipids not containing the glycerol backbone are the sphingolipids and glycosphingolipids, derived from sphingosine or dihydrosphingosine and are mainly found in nerve cells and in brain. Sphingolipids comprise ceramides and sphingomyelins, whereas glycosphingolipids can be subdivided into cerebrosides and gangliosides, both bearing carbohydrate head groups as characteristic structural elements.Animportant lipid component in eukaryotic (but not in prokaryotic) cells are the sterols with cholesterol as the principal representative.

The lipids in eukaryotic cell membranes are mainly nitrogen-containing phospholipids. They are involved in the maintenance of the barrier properties of membranes and provide the optimal conditions for transmembrane protein functioning. Some phospholipids also play a decisive role in cell signaling processes. Phosphatidic acidwas shown to enhance the membrane binding of phospholipase C-β₁ and to stimulate hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP₂), resulting in the formation of diacylglycerol and inositol 1,4,5-triphosphate. The released diacylglycerols may then further activate kinases.

Sphingolipids and glycosphingolipids are believed to be structural as well as signaling constituents of membranes. Sphingomyelin hydrolysis yields ceramide, a lipid mediator involved in regulating cell growth, cell differentiation, and cell death. Glycosphingolipids act as specific recognition sites in eukaryotic cells, and they determine blood-group, organ, and tissue specificity and are further involved in tissue immunity and cell–cell recognition.

The phospholipids found in prokaryotic (bacterial) and eukaryotic (mammalian) cell membranes usually contain saturated as well as cis-unsaturated fatty acyl chains, the most abundant being the saturated palmitoyl (C 16:0) and the cis-unsaturated oleoyl chains (C 18:1, cis). There is a strong positional preference for the two types of fatty acids, with the saturated and the unsaturated chain being localized at positions 1 and 2, respectively, of the glycerol backbone of the lipid molecule. Phospholipids with a single cis-double bond are predominant, but lipids containing more than one double bond also occur quite commonly. In membranes of the nervous system, polyunsaturated fatty acids appear to be critical for proper membrane functioning. The length of the fatty acyl chains and the degree of chain unsaturation as well as the size, the charge, and the hydrogen-bonding capacity of headgroups determine the intermolecular lipid–lipid interactions reflected in the lipid packing density and the gelto- liquid crystal phase transition temperatures of lipid membranes. The effect of headgroups on the gel-to-liquid crystal phase transition temperature, Tc, is illustrated by the following series of lipids (C 16:0) mixed withwater: PC (Tc =41°C)∼PG (Tc =41°C)∼SM (Tc =41°C)< PS deprotonated (Tc = 54°C)< PS protonated (Tc = 62°C)< PE (Tc = 64°C)< PA (Tc = 71°C)< GalCer (Tc =82°C). Knowledge of the gel-to-liquid crystal phase transitions is of relevance for the question of lipid domain formation to be discussed below.